Millions of Americans use dietary supplements with little knowledge about their benefits or risks. We examined associations of various herbal/specialty supplements with lung and colorectal cancer risk. Men and women, 50 to 76 years, in the VITamins And Lifestyle cohort completed a 24-page baseline questionnaire that captured duration (years) and frequency (days per week) of use of commonly used herbal/specialty supplements. Dose was not assessed due to the lack of accurate potency information. Supplement exposure was categorized as "no use" or "any use" over the previous 10 years. Hazard ratios (HR) were estimated by multivariate Cox regression models. Incident lung (n = 665) and colorectal cancers (n = 428) were obtained from the Surveillance, Epidemiology, and End Results cancer registry. Any use of glucosamine and chondroitin, which have anti-inflammatory properties, over the previous 10 years, was associated with significantly lower lung cancer risk: HR 0.74 [95% confidence interval (95% CI), 0.58-0.94] and HR 0.72 (95% CI, 0.54-0.96) and colorectal cancer risk: HR 0.73 (95% CI, 0.54-0.98) and HR 0.65 (95% CI, 0.45-0.93), respectively. There were also statistically significantly inverse associations of fish oil: HR 0.65 (95% CI, 0.42-0.99), methylsulfonylmethane: HR 0.46 (95% CI, 0.23-0.93), and St. John's wort: HR 0.35 (95% CI, 0.14-0.85) with colorectal cancer risk. In contrast, garlic pills were associated with a statistically significant 35% elevated colorectal cancer risk. These results suggest that some herbal/specialty supplements may be associated with lung and colorectal cancer risk; however, these products should be used with caution. Additional studies examining the effects of herbal/specialty supplements on risk for cancer and other diseases are needed